The nervous system processes sensory stimuli, such as sounds, by encoding them into a sequence of neural representations. Sound reaching the ear is converted into a pattern of spikes in the auditory nerve. This spike pattern is then relayed through a series of processing stages, or representations, until it reaches the primary auditory cortex. The cortical representation is a different, highly processed, version of the input from the auditory nerve from which it was derived. The basic goal of this proposal is to understand the synaptic and circuit mechanisms by which neurons in the primary auditory cortex transform representations of their acoustic environment. A better understanding of the mechanisms underlying the cortical transformations of peripheral inputs will have implications for sensory processing in auditory and non-auditory modalities; for learning and memory; and for the cortical consequences of hearing loss and other pathological conditions. The specific aims of our proposal are to: (1) elucidate the cortical mechanisms that establish the spectral selectivity of neurons in the primary auditory cortex; (2) elucidate the cortical mechanisms that establish the temporal selectivity of neurons in the primary auditory cortex; and (3) test whether these mechanisms are sufficient to account for neuronal responses to more complex stimuli which involve interactions between spectral and temporal properties. To achieve these aims, we will use a combination of electrophysiological, pharmacological and computational tools. In particular, we will make extensive use of in vivo whole cell patch clamp recording, a powerful technique we have successfully adapted to the rat primary auditory cortex.